Bernard Flourié

Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia : the irritable stomach syndrome

Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume ≤400 ml of air, but only one of the 20 controls (P<0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5,P<0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research.

Effects of fructo‐oligosaccharides ingestion on fecal bifidobacteria and selected metabolic indexes of colon carcinogenesis in healthy humans

Fructo-oligosaccharides (FOS) are a mixture of oligosaccharides consisting of glucose linked to fructose units. They are not digested in the human small intestine but fermented in the colon, where they could specifically promote the growth of some species of the indigenous microflora, especially bifidobacteria. We assessed in healthy humans the effects of FOS ingestion in fecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis. Twenty volunteers randomly divided into two groups were studied for three consecutive 12-day periods. During the ingestion period, they received 12.5 g/day FOS or placebo (saccharose) in three oral doses. Stools were regularly collected and analyzed. FOS ingestion led to an increase in fecal bifidobacterial counts [7.9 +/- 0.5 to 9.1 +/- 0.3 (SE) log colony-forming units/g wet wt, p < 0.01] and beta-fructosidase activity (9.6 +/- 1.9 to 13.8 +/- 1.9 IU/g dry wt, p < 0.01). In contrast, FOS ingestion had no significant effect on fecal total anaerobes, pH, the activities of nitroreductase, azoreductase, and beta-glucuronidase, and the concentrations of bile acids and neutral sterols. We conclude that ingestion of FOS, at a clinically tolerated dose of 12.5 g/day, led to an increase in colonic bifidobacteria. This effect was not associated in healthy humans with beneficial changes in various factors potentially involved in the pathogenesis of colonic cancer.

Antibiotic efficacy in small intestinal bacterial overgrowth–related chronic diarrhea: A crossover, randomized trial

BACKGROUND & AIMS No controlled trial has examined the clinical efficacy of antibiotics in small bowel bacterial overgrowth. METHODS Ten patients with bacterial overgrowth-related diarrhea underwent the following five 7-day treatment periods: untreated (control period), then placebo, and subsequently, in random order and blinded fashion, norfloxacin (800 mg/day), amoxicillin-clavulanic acid (1500 mg/day), and Saccharomyces boulardii (1500 mg/day). A hydrogen breath test was performed on the first and last day of each period. RESULTS Daily stool frequency was similar during the control and placebo periods (4.2 +/- 0.6 vs. 3.9 +/- 0.6 [mean +/- SEM], respectively). Norfloxacin and amoxicillin-clavulanic acid led to a significant reduction in daily stool frequency (2.3 +/- 0.4 and 3.0 +/- 0.5, respectively; P < 0.01 vs. placebo period) after 2.0 +/- 1.4 and 1.2 +/- 0.4 days, which was maintained for 6.1 +/- 3.7 and 6.0 +/- 9.6 days, respectively. Breath-expired H(2) volume decreased with norfloxacin (37 +/- 8 to 12 +/- 5 mL per 2 hours; P < 0.01) and amoxicillin-clavulanic acid (24 +/- 6 to 8 +/- 4 mL per 2 hours, respectively; P = 0.01), but H(2) breath test result was negative in only 3 and 5 patients. CONCLUSIONS Norfloxacin and amoxicillin-clavulanic acid are effective in the treatment of bacterial overgrowth-related diarrhea.

Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans.

Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption.

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases.

Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome.

Objective:Small intestinal bacterial overgrowth syndrome (SIBOS) is characterized by an abnormally high bacterial population level in the upper gut, exceeding 105 organisms/ml (5 log colony-forming unit (CFU)/ml). To understand its origin and select an appropriate antibiotic treatment, we have analyzed the bacterial populations contaminating the upper gut in SIBOS patients.Methods:Jejunal samples of 63 consecutive patients with diarrhea or malabsorption and conditions predisposing to SIBOS were cultured and antibiotic sensitivities determined.Results:Concentrations of total, microaerophilic, and anaerobic bacteria were confirmed in 55 patients with SIBOS (mean ± SE) 7.6 ± 0.8, 7.4 ± 0.9, and 6.1 ± 0.7 log CFU/ml, respectively. Mean number of bacterial genera was 4.6 ± 0.8. The main bacteria recovered were (mean ± SE log CFU/ml) Streptococcus (71%; 6.4 ± 0.8), Escherichia coli (69%; 7.2 ± 0.9), Staphylococcus (25%; 6.2 ± 0.6), Micrococcus (22%; 6.0 ± 0.7), Klebsiella (20%; 7.1 ± 0.8), Proteus (11%; 6.1 ± 0.8) for microaerophilic bacteria, and Lactobacillus (75%; 6.1 ± 1.1), Bacteroides (29%; 6.9 ± 1.3), Clostridium (25%; 5.5 ± 1.0), Veillonella (25%; 5.3 ± 0.7), Fusobacterium (13%; 4.8 ± 0.5), and Peptostreptococcus (13%; 6.1 ± 0.7) for anaerobic bacteria. Amoxicillin–clavulanic acid and cefoxitin were efficient on >90% of strains.Conclusions:Contaminating flora isolated in SIBOS include commonly identified oropharyngeal and colonic flora, but these occur in SIBOS at different levels from those usually found in their original location. These data may hopefully serve as a starting point to further therapeutic controlled studies.

A multicenter experience with infliximab for ulcerative colitis: outcomes and predictors of response, optimization, colectomy, and hospitalization.

OBJECTIVES:The objective of this study was to evaluate short- and long-term outcomes of infliximab in ulcerative colitis (UC), including infliximab optimization, colectomy, and hospitalization.METHODS:This was a retrospective multicenter study. All adult patients who received at least one infliximab infusion for UC were included. Cumulative probabilities of event-free survival were estimated by the Kaplan–Meier method. Independent predictors were identified using binary logistic regression or Cox proportional-hazards regression, and results were expressed as odds ratios or hazard ratios (HRs), respectively.RESULTS:Between January 2000 and August 2009, 191 UC patients received infliximab therapy. Median follow-up per patient was 18 months (interquartile range=25–75th, 8–32 months). Primary non-response was noted in 42 patients (22.0%). “Hemoglobin at infliximab initiation ≤9.4 g/dl” (odds ratio=4.35; 95% confidence interval (CI)=1.81–10.42) was a positive predictor of non-response to infliximab. Infliximab optimization was required in 36 (45.0%) of 80 patients on scheduled infliximab therapy. The only predictor of infliximab optimization was “infliximab indication for acute severe colitis” (HR=2.75; 95% CI=1.23–6.12). Thirty-six patients (18.8%) underwent colectomy. Predictors of colectomy were: “no clinical response after infliximab induction” (HR=7.06; 95% CI=3.36–14.83), “C-reactive protein at infliximab initiation >10 mg/l” (HR=5.11; 95% CI=1.77–14.76), “infliximab indication for acute severe colitis” (HR=3.40; 95% CI=1.48–7.81), and “previous treatment with cyclosporine” (HR=2.53; 95% CI=1.22–5.28). Sixty-nine patients (36.1%) were hospitalized at least one time and UC-related hospitalizations rate was 29 per 100 patient-years (95% CI=24–35 per 100 patient-years). Predictors of first hospitalization were: “no clinical response after infliximab induction” (HR=3.87; 95% CI=2.29–6.53), “infliximab indication for acute severe colitis” (HR=3.13, 95% CI=1.65–5.94), “disease duration at infliximab initiation ≤50 months” (HR=2.14, 95% CI=1.25–3.66), “hemoglobin at infliximab initiation ≤11.8 g/dl” (HR=1.77; 95% CI=1.03–3.04), and “previous treatment with methotrexate” (HR=0.30; 95% CI=0.09–0.97).CONCLUSIONS:Primary non-response to infliximab was noted in one fifth of patients and increased by seven and four the risks of colectomy and hospitalization, respectively. Infliximab optimization, colectomy, and hospitalization were required in half, one fifth, and one third of patients, respectively. Infliximab indication for acute severe colitis increased by three the risks of infliximab optimization, colectomy, and UC-related hospitalization.

Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma de novo

Background: Data concerning small bowel adenocarcinoma (SBA) in Crohns disease (CD) come from case reports and small retrospective series. The aim of this study was to further describe SBA in patients with CD and compare it with SBA de novo. Methods: Twenty patients with CD with SBA recruited in French university hospitals were studied and compared with 40 patients with SBA de novo recruited from a population‐based registry. SBA occurred after a median time of 15 years of CD and was located within the inflamed areas of the ileum (n = 19) or jejunum (n = 1), whereas in patients with SBA de novo, it was distributed all along the small intestine. Median age at diagnosis of SBA was 47 years (range, 33‐72 yr) in patients with CD and 68 years (range, 41‐95 yr) in those with SBA de novo. Results: The cumulative risk of SBA, assessed in a subgroup of patients, was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. SBA accounted for 25% and 45% of the risk of gastrointestinal carcinoma after 10 and 25 years of CD, respectively. Diagnosis was made preoperatively in 1/20 patients with CD and 22/40 patients with SBA de novo. Signet ring cells were found in 35% of patients with CD but not in patients with SBA de novo. Relative survival was not significantly different in these 2 categories of patients (54 versus 37% and 35 versus 30% in patients with and without CD at 2 and 5 yr, respectively). Conclusions: SBA in CD is different from SBA de novo. It arises from longstanding ileal inflammation and is difficult to diagnose. SBA cumulative risk increases after 10 years of CD and is likely to cause premature mortality in patients with early‐onset CD.

Lactulose ingestion increases faecal bifidobacterial counts: A randomised double-blind study in healthy humans

Objective: Faecal bifidobacteria and lactobacilli, perceived as exerting health-promoting properties, may be increased by ingestion of high-dose lactulose in humans. The effects of low and well-tolerated doses of lactulose are not well known. The aim of the study was to assess the effects of prolonged low-dose lactulose administration on faecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis.Subjects and methods: In all, 16 healthy volunteers were included in this controlled, randomised, double-blind, parallel group trial. Participants ingested lactulose or placebo (sucrose) at a dose of 5 g b.i.d. for 6 weeks. Stools were regularly collected at baseline (d0), and after 3 (d21) and 6 (d42) weeks of sugar ingestion. Tolerance was evaluated using a daily chart.Results: Faecal bifidobacterial counts were higher in lactulose than in sucrose group (P=0.03). Lactulose ingestion led to a significant increase in faecal bifidobacteria counts from d0 to d21 and d42 ((m±s.e.m.) 8.25±0.53, 8.96±0.40 and 9.54±0.28 log colony-forming units/g wet wt (CFU/g), respectively (P=0.048)). Placebo ingestion did not lead to any faecal bifidobacterial count change. Total anaerobes, Lactobacillus and pH were not significantly changed throughout the study in the two groups. Neither faecal bile acids nor neutral sterols were modified by lactulose. Excess flatus was more common in the lactulose group (P=0.03), but was very mild. Bloating and borborygmi did not differ between both the groups.Conclusions: A measure of 10 g lactulose/day increases faecal bifidobacterial counts, and lactulose fulfils the criteria requested to be considered as a prebiotic.

Effect of pectin on jejunal glucose absorption and unstirred layer thickness in normal man.

The effect of high methoxy apple pectin, a carbohydrate gelling agent, on the intestinal absorption of glucose, water, and sodium was studied in man. The effect of intraluminal fibre was evaluated in 22 healthy volunteers by the intestinal perfusion technique under an occlusive balloon. The test solutions (NaCl 130 mM, KCl 5 mM, glucose or mannitol 30 mM, PEG 4000 5 g/l) were perfused just beyond the ligament of Treitz at a rate of 10 ml/min. A 25 cm segment was studied. Three concentrations of pectin were tested: 6, 10, and 15 g/l. The effect of this pectin at two concentrations, 6 and 10 g/l, on the jejunal unstirred layer thickness was evaluated in nine other healthy subjects by an electrical technique. In mannitol solution, pectin reversed water and sodium absorption, whatever its concentration was, while in glucose solution it significantly reduced absorption of water and sodium at 10 and 15 g/l only (p less than 0.01). It significantly reduced glucose absorption at all concentrations (p less than 0.01). This reduction was found to be correlated with the solution viscosity (p less than 0.01). Pectin did not alter the glucose dependent sodium transport but increased significantly (p less than 0.001) the unstirred layer thickness. These results suggested that, in healthy man, pectin acutely given may impair intestinal absorption by means of an increased unstirred layer resistance. This effect could contribute to the diminished postprandial glycaemia observed in human subjects fed pectin.